The overall goal of this program is to examine the use of genetically modified antigen presenting cells as vaccines for both the prevention and treatment of AIDS. The primary issue that will be address is whether manipulation of the presentation of specific SIV or HIV antigens to the immune system through the engineered expression of those antigens and potential immunostimulatory gene products in different cell types might lead to more effective immune responses against SIV or HIV that other more conventional methods of vaccination. A variety of cell types with different antigen presentation properties will be transduced so as to express single or complex mixtures of viral gene products in conjunction with potential immunostimulatory gene products. The immune response to a variety of different strategies for vaccination administration will then be characterized in detail. In order to attempt to specifically model the ability of such vaccines to eradicate cellular reservoirs AIDS to mediate to either rejection of a number of will characterized murine tumors that have been engineered to express specific viral gene products, or rejection of normal CD4+ T cells expressing the viral gene products. A number of different models of immunodeficiency will be developed in order to assess the ability of specific vaccine candidates to stimulate immune responses in immunocompromised hosts. Based on the murine studies, candidate gene products and cell types will be identified, and the appropriate methods and reagents for testing cell-based vaccines in primates and man will be generated. Collaborations with other members of the NCDVG will then be established in order to compare to efficacy of the vaccines to other vaccine candidates.